Abstract:[Abstract]Objective: Based on bioinformatics, the aim of this study is to explore the mechanism of osteoarthritis miRNAmRNA regulatory network, the Hub genes would be screened and its molecular regulatory mechanism in osteoarthritis is also analysed. Methods: Through the GEO database, the miRNA microarray dataset (GSE105027) and the mRNA microarray dataset (GSE55235) of osteoarthritis were obtained, and the differentially expressed genes were analyzed. Then FunRich software was used to predict the transcription factors of differentially expressed miRNAs, functional enrichment analysis and target gene prediction, and then the predicted target genes were crossed with the differentially expressed mRNAs to obtain the miRNAmRNA regulatory network. Then the STRING database and Cytoscape software were used to construct a protein interaction network and screen out the Hub genes. Finally, R language was used to analyze the function and related pathways of Hub gene. Results: ① A total of 265 miRNAs and 838 mRNAs were shown differentially expressed; ② The prediction of 265 miRNAs resulted in a total of 203 transcription factors, of which EGR1 had the most significant difference. Enrichment analysis showed that miRNAs were mainly involved in the regulation of nucleobase, nucleoside, nucleotide and nucleic acid metabolism, cell growth regulation, transcription and other processes; ③ A total of 3 572 target genes were predicted, and the screening was based on the negative regulatory relationship between miRNA and mRNA. And 96 mRNAs and 25 miRNAs with negative regulation of cross-expression were identified; ④ JUN, FOS, IL-6, TNF, IL-1β, and CXCL8 are the Hub genes in the protein interaction network; ⑤ The enrichment analysis mainly covers biological processes such as the response to lipopolysaccharide, the response to bacteria-derived molecules, and the regulation of DNAbinding transcription factor activity, involving IL-17, Toll-like receptors, AGERAGE, TNF and NODlike receptors signaling pathways. Conclusion: The miRNAmRNA regulatory network of osteoarthritis was successfully screened and constructed, and the molecular regulation mechanism of miRNA and its target genes in the occurrence and development of osteoarthritis was clarified to a certain extent.
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